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Lecture 1 – Chapter 2 and 9Chapter 2 - EvolutionEvolution of the Human Brain Research was stimulated by the assumption that brain size and intellectual capacity are closely related but this assumption was void due to (a) humans not being the species with the largest brains on Earth (b) no indicatio...

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Lecture 1 – Chapter 2 and 9 Chapter 2 - Evolution Evolution of the Human Brain 

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Research was stimulated by the assumption that brain size and intellectual capacity are closely related but this assumption was void due to (a) humans not being the species with the largest brains on Earth (b) no indication that the most intelligent humans had larger brain than an average human brain Researchers made a point to consider the evolution of brainstem separately from the evolution of the cerebrum (cerebral hemispheres) Brainstem = regulates reflex activities that are critical for survival Cerebrum = adaptive processes such as learning, perception and motivation Comparing the human brain to the living descendants of which the human species have evolved from, three things are apparent: 1. Brain size has increased during evolution 2. Increase in size has occurred in the cerebrum mostly 3. Folds on the cerebral surface also known as the “convolutions” greatly increased the surface area of the cerebral cortex which is the outermost layer of the cerebral tissue

Chapter 9 - Development of the Nervous System The brain is not a static network of interconnected elements. It is a plastic – changeable, living organ that continuously changes in response to its genetic programs and environment. Experiences as well development of the brain are essential for normal neurological processes to take place.

Five phas phases es o off Neu Neurode rode rodevelop velop velopmen men mentt The union of an ovum and a sperm makes a zygote. The zygote then divides to form two daughter cells. These two divide to form four and so on and so forth unlike a mature organism is produced. Along with cell multiplication, three other things occur to ensure human development, and these are:

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Cell differentiation – differentiating themselves into muscle cells, multipolar neurons, glial cells etc. Cell migration – they transport themselves to appropriate sites and align themselves with the cells around them to form structures. Cell establishment – where they establish appropriate functional relations with other cells.

These three things are accomplished via developing neurons through five phases and these are: 1. Induction of the Neural Plate  3 weeks after conception, the tissue that is destined to develop into human nervous system becomes recognized as the neural plate – a small patch of ectodermal tissue on the dorsal surface of the developing embryo  Embryonic cells have three layers – ectoderm, mesoderm and endoderm.  The development of the neural plate is the first major stage of neurodevelopment in all vertebrates and it is induced by chemical signals from an area of the underlying mesoderm layer (organizer)  The cells of neural plate are often referred to as embryonic stem cells which are (a) unlimited capacity for self-renewal if maintained in an appropriate cell culture and (b) develop into many kinds of cells.  Neural plate then folds to form the neural groove which fuses to form the neural tube.  Inside of the neural tube eventually becomes the cerebral ventricles and the spinal cord.  After 40 days of conception – 3 swellings are visible at the anterior end of the human neural tube; these develop into the forebrain, mid brain and hindbrain.

2. Neural Proliferation  After the fusion of the neural grove into neural tube, the cells of the tube begin proliferating (increase greatly in number)  Proliferation is not equal in all parts, most cell division in the tube occurs in the ventricular zone (fluid-filled center of the tube)  Proliferation is controlled by chemical signals from two organizer areas in the neural tube: floor plate and the roof plate 3. Migration and Aggregation  After cell division in the ventricular zone, cells then migrate to appropriate zones. Time and location play a major role in this period of migration  Two kinds of cell migration occur in the developing neural tube and these are radial migration and tangential migration.  Two methods by which developing cells migrate are somal translocation – extension grows from the developing cell in the direction of the migration and the cell body moves and follows that direction. Glial-mediated migration occurs when the proliferation is under way and the walls of neural tube are thickening, glial cells aka radial cells appear in the developing neural tube. Radial migration is facilitated.

Aggregation – developing neurons migrated, they align themselves with other developing neurons that have migrated to the same area to form the structures of the nervous system. 4. Axon Growth and Synapse Formation  Axons and dendrites begin to grow from the neurons that have migrated. These projections are important for the function of nervous system  Growth cone at the tip of each axon and dendrite extends and retracts fingerlike cytoplasmic extensions called filopodia as if searching for the correct route.  Once axons have reached their intended sires, they must establish an appropriate pattern of synapses.  A single neuron can grow an axon on its own but to grow a synapses in between two neurons requires coordinated activity. 

Synapse formation requires glial cells. Developing neurons need high levels of cholesterol during synapse formation and the cholesterol is typically supplied by the astrocytes in the glial cells.  Astrocytes are also helpful due to their role in processing, transferring and storing information supplied by neurons. 5. Neuron Death and Synapse Rearrangement  Neuron death is a normal and an important part of neurodevelopment. Genetic programs inside neurons are triggered and cause them to actively complete suicide, this process is called apoptosis  Apoptosis is triggered by (a) developing neurons are genetically programmed for early death (b) due to not being able to obtain life-preserving chemicals that are supplied by their targets.  Cell death results in a massive rearrangement of synaptic connections. 

Lecture 2 – Chapter 3 Chapter 3 – Anatomy of the Nervous System Divis Divisions ions of th the e Ner Nervous vous Syst System em 

Composed of two divisions; central nervous system (skull; brain and spine; spinal cord) and peripheral nervous system (rest of it).

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The CNS is encased in bone and it is covered by three protective membranes called the meninges. Outer layer – meninx is a tough membrane called the dura mater (tough mother).

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Second layer – inside dura mater is the arachnoid membrane (spider-web-like). Beneath the arachnoid membrane, there is a subarachnoid space which contains many large blood vessels and cerebrospinal fluid Inner layer – delicate pia mater (pious mother) which adheres to the surface of the CNS.

Ven Ventricles tricles and Cereb Cerebrospi rospi rospinal nal Flu Fluid id   

Cerebrospinal fluid (CSF) also protects the CNS. It fills the subarachnoid space, the central canal of the spinal cord and the cerebral ventricles of the brain which are all interconnected. Central canal – small central channel that runs the length of the spinal cord Cerebral ventricles – four large internal chambers of the brain (two lateral, third and fourth)

Cells of th the eN Nervous ervous Sys System tem Two fundamentally different type of cells are what the nervous system consists of and these are: 1. Neurons  Cells that are specialized for the reception, conduction and transmission of electrochemical signals.

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The neuron cell membrane is composed of a lipid bilayer or two layers of fat molecules. In the lipid bilayer; numerous protein molecules that are the basis of many of the cell membrane’s functional properties. Membrane proteins are (a) channel protein through which certain molecules can pass (b) signal proteins which transfer a signal to the inside of the neuron when molecules bind to them on the outside of the membrane.

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Neurons can be classified based on the number of processes emanating from their cell bodies Multipolar – more than 2 processes extending from its cell body Unipolar – only one process extending from its cell body Bipolar – only two processes Interneuron – neurons with a short or no axon are called this. Function is to integrate neural activity within a single brain structure, not to conduct signals from one structure to another. Nervous system = two neural structures (a) composed of cell bodies (b) composed of axons In CNS – clusters of cell bodies are called nuclei whereas in PNS – ganglia. In CNS – bundles of axons are called tracts whereas in PNS – nerves.

2. Glial Cells  Equal number of glial and neurons in the human brain  Several kinds of glial cells such as: - Oligodendrocytes: glial cells with extensions that wrap around the axons of some neurons of the CNS. Extensions rich in myelin (fatty insulation) and the myelin sheaths they form increase the speed and efficiency of axonal conduction. - Schwann cells: located in the PNS, constitutes of one myelin segment unlike oligodendrocytes. Guide axonal regeneration after damage. - Microglia: Smaller than other glial cells. Respond to injury or disease by multiplying, engulfing cellular debris or even entire cells and triggering inflammatory responses. - Astrocytes: Largest glial cells, star shaped hence the name. Extensions of astrocytes cover the outer surface of blood vessels that course through the brain. They also contact neurons. They allow the passage of some chemicals from blood to CNS neurons and blockage as well. Can contract or relax blood vessels based on the blood flow demands.

An Anatomy atomy of th the e Br Brain ain

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To understand a fully functioning adult human brain, it is important to understand the initial human brain development during embryonic growth. At this stage of brain development, there are three swellings that occurs at the anterior end of the neural tube and these swellings eventually develop into the forebrain, midbrain and hindbrain. Before birth, the initial three swellings in the tube become five (2 in forebrain and 2 in hindbrain). From anterior to posterior, the 5 swellings that compose the developing brain at birth are the:

1. Myelencephalon (Medulla) - Hindbrain  Most posterior division of the brain.  Composed largely of tracts carrying signals between the rest of the brain and body  Contains the reticular formation which plays a role in arousal. Included in a variety of functions such a sleep, attention, movement, maintenance of muscle tone and various cardiac, circulatory and respiratory reflexes. 2. Metencephalon (Brainstem; Pons and Cerebellum) – Hindbrain  Houses many ascending and descending tracts and part of the reticular formation.  Structures create a bulge, called the pons, on the brain stem’s ventral surface. Pons and cerebellum are the major divisions of the metencephalon.  Cerebellum is the large, convoluted structure on the brain stem’s dorsal surface.  Important sensorimotor structure; cerebellar damage eliminates the ability to precisely control one’s movements and to adapt them to changing conditions 3. Mesencephalon – Midbrain  Two divisions and these are (a) tectum and (b) tegmentum.  Tectum – dorsal surface of the midbrain. Composed of two pairs of bumps (colliculi), (a) inferior colliculi is the posterior pair which has an auditory function and (b) superior colliculi is the anterior pair which has a visual-motor function.  Tegmentum – division of the mesencephalon ventral to the tectum. Contains three colorful structures; 1) the periaqueductal gray - gray matter situated around the cerebral aqueduct, the duct connecting the third and fourth ventricle

2) the substantia nigra 3) the red nucleus.  Substantia nigra and red nucleus are important components of the sensorimotor system 4. Diencephalon – Forebrain  Composed of two structures: 1) Thalamus - large, two-lobed structure that constitutes the top of the brain stem. - One lobe sits on each side of the third ventricle, and two lobes are joined by the massa intermedia, which runs through the ventricle. - White lamina (layers) are visible on the surface of the thalamus that are composed of myelinated axons. - Comprises of many different pairs of nuclei, most of which project to the cortex. - Sensory relay nuclei – nuclei that receive signals from sensory receptors, process them and then transmit them to the appropriate areas of the sensory cortex 2) Hypothalamus - Located just below the anterior thalamus. Plays an important role in the regulation of several motivated behaviours. - Exerts its effects in part by regulating the release of hormones from the pituitary gland - Optic chiasm – where the optic nerves from each eye come together. The X shape is created because some of the axons of the optic nerve decussate (cross over to other side of the brain) via the chiasm. - Mammillary bodies – pair of spherical nuclei located on the inferior surface of the hypothalamus, just behind the pituitary. 5. Telencephalon – Forebrain  Largest division of the brain which mediates the brain’s most complex functions.  Initiates voluntary movement, sensory input and complex cognitive processes such as learning, speaking and problem solving  Cerebral hemispheres are covered by a layer of tissue called the cerebral cortex.  Cerebral cortex composed of small, unmyelinated neurons, it is gray and is referred to as the gray matter  Layer beneath the cortex is composed of myelinated axons which are white and referred to as the white matter  Cerebral cortex is deeply convoluted, and these convolutions have the effect of increasing the amount of cerebral cortex without increasing the overall volume of brain.  The large furrows are called fissures and the small ones are called sulci and the ridges in between them are called gyri.  Hemispheres are separated by the largest fissure called the longitudinal fissure  Hemispheres are connected by a few tracts called cerebral commissures and the largest one of them is called the corpus callosum  Central fissure and lateral fissure divide each hemisphere into four lobes: frontal, parietal, temporal and occipital. Among the gyri are the precentral gyri, postcentral gyri and the superior temporal gyri  Occipital lobe – Responsible for the input of visual stimuli.

 Parietal lobe – Postcentral gyrus analyzes the sensations from the body. Posterior parts of the lobe play roles in perceiving location of both objects and the person itself.  Temporal lobe – superior temporal gyrus is responsible for hearing and language. Inferior temporal cortex identifies complex visual patterns. Medial temporal cortex is important for certain kinds of memory  Frontal lobe – precentral gyrus and adjacent frontal cortex have a motor function. Frontal cortex anterior to the motor cortex performs complex cognitive functions such as planning response sequences, evaluating the outcomes of behaviour etc.  Hippocampus is one important area of cortex that is not neocortex – three major layers. Located at the medial edge of the cerebral cortex as it folds back on itself in the medial temporal lobe. Seahorse shaped folds in a cross section. Plays a role in memory (spatial location)

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Limbic System: - Circuit of midline structures that circle the thalamus. Involved in the regulation of motivated behaviours – fleeing, feeding, fighting and sexual behaviour. - Major structures include mammillary bodies and the hippocampus, amygdala, fornix, cingulate cortex and septum - Amygdala – almond shaped nucleus in the anterior temporal lobe. Posterior to the amygdala is the hippocampus, which runs beneath the thalamus in the medial temporal love. - Cingulate cortex – large strip of cortex in the cingulate gyrus on the medial surface of the cerebral hemispheres, superior to the corpus callosum. Encircles the dorsal thalamus - Fornix – major tract of the limbic system, also encircles the dorsal thalamus. Leaves the dorsal end of the hippocampus and sweeps forward in an arc coursing along the superior surface of the third ventricle and terminating in the septum and mammillary bodies - Septum – midline nucleus located at the anterior tip of the cingulate cortex

 Basal Ganglia - long tail-like caudate sweeping out of each amygdala. - Each caudate forms an almost complete circle, in its center, connected to it by a series of fiber bridges is the putamen. - Putamen + caudate = striatum - Globus pallidus – located medial to the putamen between the putamen and thalamus - BG plays a role in performance of voluntary motor responses and decision making

Lecture 3 & 4 – Chapter 4 Chapter 4 – Neural Conduction and Synaptic Transmission Ionic Bas Basis is of the Re Resting sting Poten Potential tial     

Salts in neural tissue separate into positively and negatively charged particles called ions Many kinds of ions in neurons, but two important ones are Na+ and K+. In resting neurons – more Na+ ions outside the cell than inside and more K+ ions inside than outside. Each type of ion channel is specialized for the passage of ions. Two types of pressure that drive to the ions to enter or exit and these are (a) electrostatic pressure and (b) concentration gradient Ion transport is performed by mechanisms in the cell membrane that continually exchange three Na+ inside the neuron for two K+ outside. These transporters are commonly referred to as sodium-potassium pumps

Gen Generati erati eration on an and d Con Conduc duc duction tion o off Pos Postsynap tsynap tsynaptic tic Poten Potentials tials 

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When neurons fire, they release chemicals called neurotransmitters, which diffuse across the synaptic clefts and interact with specialized receptor molecules on the receptive membranes of the next neurons in the circuit Two effects, depending on the neurotransmitter occur when it binds to postsynaptic receptor: 1) Can depolarize the receptive membrane (decreasing resting membrane potential, making it more positive). Called excitatory postsynaptic potentials (EPSPs) because they increase the likelihood of neuron firing 2) Can hyperpolarize (increasing resting membrane potential, making it more negative). Called inhibitory postsynaptic potentials (IPSPs) because they decrease the likelihood of neuron firing. EPSPs and IPSPs are graded responses – means that amplitudes are proportional to the intensity of the signals that elicit them Postsynaptic potential transmission has two characteristics:

1) Rapid, almost instantaneous. 2) Decremental, decrease in amplitude as they travel through the neuron, just as sound wave loses amplitude.

Integ Integrati rati ration on of PPosts osts ostsynap ynap ynaptic tic PPotenti otenti otentials als an and dG Genera enera eneration tion o off Ac Action tion PPotent otent otentials ials   

Action potentially were thought to be generated at the axon hillock however, they are generated in the adjacent section of the axon, called the axon initial segment. An action potential is generated if the membrane is depolarized to a level referred to as its threshold of excitation (-65mV) Multipolar neurons add together all the graded EPSPs and IPSPs reaching its axon and decides to fire or not to fire based on their sum, this process is called integration and it happens over time (temporal summation) and over space (spatial summation).

Temporal Summation (over time)

Spatial Summation (over space)

Cond Conduct uct uction ion o off Action Po Potent tent tentials ials It is through voltage-activated ion channels that close and open in response to changes in the level of MP that facilitates the production and conduction of an action potentials. 1. Ionic basis of action potentials  Membrane potential is at rest is constant although there is pressure to drive Na+ inside the cell. This is because resting memb...